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With sodium iodide; potassium carbonate; In dichloromethane; water; acetone; |
EXAMPLE 16 4-[1-(Ethoxycarbonyloxy)ethoxy]-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-Dioxide To a round bottomed flask equipped with a reflux condenser and stirring bar were added piroxicam (10.0 g, 30.2 mmol), potassium carbonate (8.35 g, 60.4 mmol), alpha-chloroethyl ethyl carbonate (12.35 mL, 13.81 g, 90.6 mmol) and acetone (350 mL). The heterogenous reaction mixture was heated to reflux under a nitrogen atmosphere. After 19 hours, anhydrous sodium iodide (22.6 g, 150.7 mmol) was added and reflux continued for an additional 5 hours. The acetone was removed in vacuo leaving a brown residue which was treated with water (250 mL) and methylene chloride (250 mL). The organic layer was separated and the aqueous layer extracted with additional methylene chloride (250 mL). The combined organic extracts were washed with water (250 mL), brine (250 mL), dried (Na2 SO4) and concentrated in vacuo to a brown oil. Column chromatography on silica gel (1:9 ethyl acetate:methylene chloride) afforded a pale yellow foam (10.67 g, 79.0percent). This was recrystallized from toluene to give 9.50 g of pure white crystals: mp 159°-161° C.; IR (KBr) 1757, 1676 cm-1; 1 H NMR (CDCl3) delta 1.16 (t, J=7.5 Hz, 3H), 1.76 (d, J=5 Hz, 3H), 3.11 (s, 3H), 4.07 (q, J=7.5 Hz, 2H), 6.35 (q, J=5 Hz, 1H), 7.11 (m, 1H), 7.67-7.80 (m, 3H), 7.86-7.93 (m, 2H), 8.36 (m, 2H), 9.40 (br s, 1H); precise mass calcd for C20 H21 N3 O7 S m/e 447.1108, found 447.1164. |